Directed Ortho-Metalation of the Three Methyl Anisoles in Various Media
type: CreativeWork
description: Directed ortho-metalation (DoM) is a very useful alternative to electrophillic aromatic substitution (EAS) for the synthesis of substituted aromatic compounds. DoM is highly regiospecific providing metalation chiefly in the ortho-position. However, lateral (a-) metalation of an alkyl side-chain and ortho-metalation of a second ortho-position can compete. Investigation of the three methylanisoles was therefore undertaken to determine the interplay between these factors and to discover metalation conditions to achieve selectivity. This goal was uniquely achieved for p-methylanisole where conditions were discovered which allowed > 85% ortho-metalation as determined by GC analysis with virturally no competing lateral metalation. Three derivitives of this ortho-lithio intermediate were prepared, each in > 75% yield. Metalation conditions were found that permitted significant descrimination between 2- and 6- position metalation of m-methylanisole. Metalation conditions were also found that permitted regiospecific a-metalation of o-methylanisole.
abstract: Directed ortho-metalation (DoM) is a very useful alternative to electrophillic aromatic substitution (EAS) for the synthesis of substituted aromatic compounds. DoM is highly regiospecific providing metalation chiefly in the ortho-position. However, lateral (a-) metalation of an alkyl side-chain and ortho-metalation of a second ortho-position can compete. Investigation of the three methylanisoles was therefore undertaken to determine the interplay between these factors and to discover metalation conditions to achieve selectivity. This goal was uniquely achieved for p-methylanisole where conditions were discovered which allowed > 85% ortho-metalation as determined by GC analysis with virturally no competing lateral metalation. Three derivitives of this ortho-lithio intermediate were prepared, each in > 75% yield. Metalation conditions were found that permitted significant descrimination between 2- and 6- position metalation of m-methylanisole. Metalation conditions were also found that permitted regiospecific a-metalation of o-methylanisole.
author: Friesen, Carl
keywords: Chemistry
date published: 1996-08-01T07:00:00Z
date modified: 2026-07-24T06:07:54Z
provider: Western Kentucky University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Western Kentucky University